ArticleThe Journal of clinical investigation2021
Integrative methylome-transcriptome analysis unravels cancer cell vulnerabilities in infant MLL-rearranged B cell acute lymphoblastic leukemia.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- DNA methylation-based classification of hematolymphoid neoplasms.Blood advances · 2026Article
- A microRNA expression signature in infant t(4;11) KMT2A::AFF1+ BCP-ALL uncovers novel therapeutic targets.HemaSphere · 2026Article
- Unraveling the molecular landscape of Erdheim-Chester disease: new insights from methylome and transcriptome integration.Leukemia · 2025Article
- Comprehensive Epigenome-Wide Profiling Reveals Distinctive DNA Methylation Signatures and Potential Prognostic Biomarkers in Mexican Pediatric B-ALL.International journal of molecular sciences · 2025Article
- Rapid epigenomic classification of acute leukemia.Nature genetics · 2025Article
- Age-Driven Genetic and Epigenetic Heterogeneity in B-ALL.International journal of molecular sciences · 2025Review
- Review
- Integration of multi-omics layers empowers precision diagnosis through unveiling pathogenic mechanisms on maple syrup urine disease.Journal of inherited metabolic disease · 2025Article
- A brain organoid/ALL coculture model reveals the AP-1 pathway as critically associated with CNS involvement of BCP-ALL.Blood advances · 2024Article
- Activating mutations remodel the chromatin accessibility landscape to drive distinct regulatory networks inHemaSphere · 2024Article
- Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation.Journal of molecular biology · 2024Review
- ELF4 was a prognostic biomarker and related to immune infiltrates in glioma.Journal of Cancer · 2024Article
- Epigenomic mapping reveals distinct B cell acute lymphoblastic leukemia chromatin architectures and regulators.Cell genomics · 2023Article
- Multi-omic integration of DNA methylation and gene expression data reveals molecular vulnerabilities in glioblastoma.Molecular oncology · 2023Article
- AP-1 Transcription Factor Complex MembersHemaSphere · 2023Article
- Histone acetylation by HBO1 (KAT7) activates Wnt/β-catenin signaling to promote leukemogenesis in B-cell acute lymphoblastic leukemia.Cell death & disease · 2023Article
- Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy.NPJ precision oncology · 2022Article
- Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia.Nature communications · 2022Article
- Hypoxic, glycolytic metabolism is a vulnerability of B-acute lymphoblastic leukemia-initiating cells.Cell reports · 2022Article
- Increasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and Aging.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 4 countries.
Funding
Abstract
B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. As predicted by its prenatal origin, infant B-ALL (iB-ALL) shows an exceptionally silent DNA mutational landscape, suggesting that alternative epigenetic mechanisms may substantially contribute to its leukemogenesis. Here, we have integrated genome-wide DNA methylome and transcriptome data from 69 patients with de novo MLL-rearranged leukemia (MLLr) and non-MLLr iB-ALL leukemia uniformly treated according to the Interfant-99/06 protocol. iB-ALL methylome signatures display a plethora of common and specific alterations associated with chromatin states related to enhancer and transcriptional control in normal hematopoietic cells. DNA methylation, gene expression, and gene coexpression network analyses segregated MLLr away from non-MLLr iB-ALL and identified a coordinated and enriched expression of the AP-1 complex members FOS and JUN and RUNX factors in MLLr iB-ALL, consistent with the significant enrichment of hypomethylated CpGs in these genes. Integrative methylome-transcriptome analysis identified consistent cancer cell vulnerabilities, revealed a robust iB-ALL-specific gene expression-correlating dmCpG signature, and confirmed an epigenetic control of AP-1 and RUNX members in reshaping the molecular network of MLLr iB-ALL. Finally, pharmacological inhibition or functional ablation of AP-1 dramatically impaired MLLr-leukemic growth in vitro and in vivo using MLLr-iB-ALL patient-derived xenografts, providing rationale for new therapeutic avenues in MLLr-iB-ALL.
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Registered trials
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